Depression is a tricky beast. Symptoms vary widely from person to person, as does the response to treatment. But there’s no question that genetic makeup plays an important role, and understanding the genetic architecture of depression could help us better understand how to treat it.

A new study in the journal Nature Geneticshas identified 44 genetic variants that can increase the risk of developing major depression. The authors of the study, which examined the genes of nearly 500,000 people, say their work suggests that all humans may carry at least some of these variants. The largest study of its kind, the work refines our understanding of the complex ways that genetics impacts mental illness.

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Previous studies have identified only a handful of variants associated with depression. In the new study, 30 of the variants identified were new. To identify them, more than 200 scientists working with the Psychiatric Genomics Consortium conducted what’s known as a genome-wide association study, scanning the genomes of 135,458 people with depression and 344,000peoplewithout depression to identify variants associated with major depression. The variants were linked to the regions of the brain targeted by some antidepressant drugs. The data sets used by the researchers came from people primarily of European descent, but researchers contrasted European results with a study of depression and genetics in Han Chinese population. (The lack of overlap in relevant variants between the two populations highlights the ongoing need for more diversity in genetic research.)

The genetic basis of mental illness is relatively poorly studied. The new study found that depression’s genetic roots are shared with one disorder that has been especially well-studied genetically, schizophrenia.

Major depression affects some 14 percent of the global population, and yet only about half of patients respond well to existing treatments. The study is an early step to more fully understanding the disorder, but identifying the molecular underpinnings could explain why some patients respond to treatment while others don’t, as well as point the way to new therapies.